Convalescent Plasma to Treat COVID-19: A Two-Center, Randomized, Double-Blind Clinical Trial.

Background: The use of convalescent plasma (CP) has been considered for its immunological mechanisms that could benefit patients in moderate and severe stages of COVID-19. This study evaluated the safety and efficacy of the use of donor CP for COVID-19. Material and methods: A double-blind, randomized controlled clinical trial was conducted from May to October 2020. Thirty-nine participants with moderate (II) and severe (III) stages of COVID-19 confirmed by RT-PCR were included. The study randomization rate was set at 3:1. CPs were chosen for application with a neutralizing antibody titer of ≥1:32. Results: We observed a significantly lower 21-day post-transfusion mortality HR: 0.17 (95.0% CI [0.07−0.45, p < 0.001]) in the group receiving CP compared with the control group; protective units (PU) in the group receiving convalescent plasma after seven days were significantly higher (512 (32−16,384) vs. 96 (32−256), p = 0.01); the PAO2/FIO2 index showed a significant improvement in the group receiving CP (251.01 (109.4) vs. 109.2 (62.4), p < 0.001, in the control group). Conclusion: CP is safe and effective, as it decreased mortality in the CP group compared with the control group.

Suppressive neutrophils require PIM1 for metabolic fitness and survival during chronic viral infection.

The immune response to a chronic viral infection is uniquely tailored to balance viral control and immunopathology. The role of myeloid cells in shaping the response to chronic viral infection, however, is poorly understood. We perform single-cell RNA sequencing of myeloid cells during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection to address this question. Our analysis identifies a cluster of suppressive neutrophils that is enriched in chronic infection. Furthermore, suppressive neutrophils highly express the gene encoding Proviral integration site for Moloney murine leukemia virus-1 (PIM1), a kinase known to promote mitochondrial fitness and cell survival. Pharmacological inhibition of PIM1 selectively diminishes suppressive neutrophil-mediated immunosuppression without affecting the function of monocytic myeloid-derived suppressor cells (M-MDSCs). Decreased accumulation of suppressive neutrophils leads to increased CD8 T cell function and viral control. Mechanistically, PIM kinase activity is required for maintaining fused mitochondrial networks in suppressive neutrophils, but not in M-MDSCs, and loss of PIM kinase function causes increased suppressive neutrophil apoptosis.

Unusual prevalence of high-risk genotypes of human papillomavirus in a group of women with neoplastic lesions and cervical cancer from Central Mexico.

Human papillomavirus has been identified as a main etiological agent in the development of cervical cancer. HPV 16 and 18 have been reported the most widely prevalent genotypes worldwide. We conducted a study analyzing the prevalence of high and low risk human papillomavirus viral types in the Mexican state of Aguascalientes and neighboring cities in the states of Jalisco and Zacatecas in central Mexico. Specific viral genotype was determined by a PCR and hybridization-based detection test. The presence of 37 high- and low-risk HPV genotypes was evaluated in 883 female participants. Of these, 350 presented low-grade squamous intraepithelial lesions (LGSIL), 176 presented high-grade squamous intraepithelial lesions (HGSIL), 107 suffered from cervical cancer and 250 women with negative cytological report for intraepithelial lesion or malignancy (NILM). HPV 51 was the most prevalent genotype, followed by HPV 16: overall prevalence of HPV 51, including single infections and co-infections was 31.2% in women with LGSIL, whereas prevalence of HPV 16 was 25.1%. Among women with HGSIL, HPV 51 prevalence was 47.2% and HPV 16 was 30.1%. Prevalence of HPV 51 in women with cervical cancer was 49.5% and type 16 was 33.6%. Between single and co-infections, most co-infections were not associated with later stages of the disease, except 51/16 and some others. HPV 51 showed a significant correlation with the progression of the disease (OR = 10.81 for LGSIL, 19.38 for HGSIL and 22.95 for ICC), and when analyzing all other genotypes, five different groups depending on their correlation with all lesion grades were determined. According to our findings, HPV genotype 51 has a higher prevalence than HPV 16 and 18 in the Mexican state of Aguascalientes and neighboring cities in the states of Jalisco and Zacatecas in Central Mexico.

Structure-function analysis of manganese exporter proteins across bacteria.

Manganese (Mn) is an essential trace nutrient for organisms because of its role in cofactoring enzymes and providing protection against reactive oxygen species (ROS). Many bacteria require manganese to form pathogenic or symbiotic interactions with eukaryotic host cells. However, excess manganese is toxic, requiring cells to have manganese export mechanisms. Bacteria are currently known to possess two widely distributed classes of manganese export proteins, MntP and MntE, but other types of transporters likely exist. Moreover, the structure and function of MntP is not well understood. Here, we characterized the role of three structurally related proteins known or predicted to be involved in manganese transport in bacteria from the MntP, UPF0016, and TerC families. These studies used computational analysis to analyze phylogeny and structure, physiological assays to test sensitivity to high levels of manganese and ROS, and inductively coupled plasma-mass spectrometry (ICP-MS) to measure metal levels. We found that MntP alters cellular resistance to ROS. Moreover, we used extensive computational analyses and phenotypic assays to identify amino acids required for MntP activity. These negatively charged residues likely serve to directly bind manganese and transport it from the cytoplasm through the membrane. We further characterized two other potential manganese transporters associated with a Mn-sensing riboswitch and found that the UPF0016 family of proteins has manganese export activity. We provide here the first phenotypic and biochemical evidence for the role of Alx, a member of the TerC family, in manganese homeostasis. It does not appear to export manganese, but rather it intriguingly facilitates an increase in intracellular manganese concentration. These findings expand the available knowledge about the identity and mechanisms of manganese homeostasis proteins across bacteria and show that proximity to a Mn-responsive riboswitch can be used to identify new components of the manganese homeostasis machinery.

Relevancia del antecedente de absceso perirrenal en pacientes sometidos a nefrectomía simple retroperitoneal / Relevance of Perirenal Abscess in Patients undergoing Retroperitoneal Simple Nephrectomy

Las infecciones supurativas del riñón y del espacio perinefrítico son poco comunes, sin embargo, se asocian a una morbimortalidad elevada, afectando a ambos sexos por igual excepto los casos de absceso cortical que es 3 veces más común en el hombre que en la mujer. La incidencia se incrementa con la edad y habitualmente se asocia a uropatía obstructiva. Los abscesos renales representan 0,2% de todos los abscesos intraabdominales, de los cuales el 10% de los abscesos corticales rompen a través de la cápsula formando un absceso perinefrítico, el cual es difícil de manejar y conlleva un peor pronóstico, con una alta mortalidad a pesar de tratamiento quirúrgico oportuno

Supurative infections of the kidney and perinephritic space are rare, however, are associated with high morbidity and mortality, affecting both sexes equally except for cases of cortical abscess which is 3 times more common in men than in women. The incidence increases with age and is usually associated with obstructive uropathy. Renal abscesses represent 0.2% of all abscesses. intraabdominal, of which 10% of cortical abscesses break through the capsule forming a Perinephritic abscess, which is difficult to manage and leads to a worse prognosis, with high mortality despite prompt surgical treatment.

[Comparison of results of open simple nephrectomy secondary to lithiasis in patients with and without nephrostomy]. / Comparación de los resultados de la nefrectomía simple abierta secundaria a litiasis en pacientes con y sin nefrostomía.

BACKGROUND: Simple nephrectomy is the procedure of choice in the treatment of excluded kidneys. The purpose of this study was to describe and compare surgical results in open simple retroperitoneal nephrectomies in patients with and without nephrostomy. METHODOLOGY: 58 patients were analyzed. The demographic parameters of patients with nephrostomy were compared to patients without nephrostomy (age, gender, weight, lithium localization, transoperative variables (surgical time, transoperative bleeding) and postoperative variables (need for intensive care, need for transfusion, surgical wound infection and hospital stay days) RESULTS: Statistically significant differences were found for the variables of operative bleeding (p=0.0442), surgical time (p=0.0093), hospital stay days (p=0.0040), and transfusion requirements (p=0.0170). There were no differences in the need for intensive care (p=0.6314), transoperative complications (p=0.7414) and surgical wound infection (p=0.2762). CONCLUSIONS: The presence of a nephrostomy catheter in patients undergoing open simple nephrectomy leads to an increased risk of morbidity, with increased bleeding, surgical time, need for transfusion, and hospital stay days.

An unusual cause of bilioenteric anastomotic dysfunction after iatrogenic bile duct injury.

Roux en Y hepatojejunostomy is the surgery of choice for bile duct repair. Anastomotical dysfunction after reconstruction has several etiopathologies. Besides technical factors, ischemia of the duct is responsible for late obstruction. Bile colonization with secondary stones and sludge can also be identified as a cause. An unusual cause of anastomotical dysfunction secondary to ascaris biliary infestation after biliary reconstruction is reported herein. The patient had intermittent cholangitis and eosinophilia. At operation, the worm was found obstructing the anastomosis.